The myelin-associated glycoprotein (MAG) is localized in the periaxonal membranes of PNS and CNS myelin sheaths where it appears to be involved in glia-axon interactions. MAG is a member of the immunoglobulin gene superfamily along with other neural adhesion proteins, and alternatives of its mRNA generates two developmentally regulated isoforms with differing C-terminal tails. The longer isoform (L-MAG) is the principal form synthesized during active myelination early in CNS development, whereas the shorter isoform (S-MAG) is the principal form synthesized in the PNS at all ages. MAG is phosphorylated both in the CNS and PNS, but the sites of phosphorylation by oligodendrocytes and Schwann cells differ. The extracellular domains of the two forms of MAG are identical with 5 immunoglobulin-like domains and 8 potential sites for N-linked glycosylation. The carbohydrate consists of a mixture of neutral and negatively charged, complex oligosaccharides whose structures are now under detailed investigation. MAG appears to be abnormally glycosylated in dysmyelinating quaking mice. The expression of MAG in cultured oligodendrocytes and Schwann cells is being studied with the ultimate objectives of identifying factors that control its synthesis and probing its function in cell-cell interactions. Cultured oligodendrocytes from adult bovine brain constitutively express a substantial amount of MAG on their surface. Although cultured Schwann cells do not normally express MAG in the absence of neurons, an immortalized Schwann cell line generated in our laboratory expresses a remarkably high level of MAG but little or none of the major myelin proteins. Furthermore, the posttranslational glycosylation, sulfation and phosphorylation of MAG occurring in these immortalized cells is similar to that in vivo, and this continuous cell line expressing a lot of MAG on its surface should be useful for investigating the cell biology and function of this glycoprotein. MAG and other myelin proteins were studied during the demyelination and remyelination occurring following cuprizone treatment of mice. Finally, a novel autoantibody was identified in an apparently normal rabbit that specifically reacts with the shorter isoform of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP).